MODEL SYSTEMS SHARED RESOURCE: TRANSGENIC MOUSE FACILITY (TMF) PROJECT SUMMARY/ABSTRACT The Transgenic Mouse Facility (TMF) provides Cancer Center members the ability to introduce manipulated genes and delete or modify endogenous genes in the germline of animals for Cancer Center members. This is a major technological advance in biology, enabling investigators to answer questions about gene function, which often must be analyzed in a whole animal model system. The TMF under the direction of Dietmar Kappes, PhD (BCDF) and 2.0 FTE staff have provided knockout animals that have been instrumental in providing insights into mechanisms of developmental gene regulation, cellular interactions within the immune system, and the effect of oncogenes on growth and differentiation. 22 Cancer Center members used the TMF in calendar year 2014. 95% of TMF users during 2014 were supported by peer-reviewed funding. 29 Cancer Center members from all 5 Research Programs used the TMF in the period 2011-2014. Additionally, TMF services are available to investigators at the Wistar Institute and Thomas Jefferson University (TJU). Since 2012, the TMF has provided service to 6 peer-review funded investigators from Wistar, and 2 peer reviewed funded investigators from TJU. Kappes' years of experience and expertise is key in implementing state-of-the- art technology and innovative approaches. Under Kappes' leadership coupled with institutional investment of $81,498 TMF capabilities were improved by purchasing a new inverted microscope with Differential Interference Contrast (DIC) optics, new micromanipulators for handling and injecting embryos, and a Hamilton Thorne laser drilling system. The TMF has utilized zinc finger nuclease (ZFN)-mediated gene targeting extensively and has recently added and validated the capacity to use CRISPR-mediated gene targeting. These approaches considerably accelerate and simplify the generation of knockout and knock-in mice, and allow generation of complex mouse models with multiple genetic alterations that were not previously feasible. Due to the complexity of the services provided and the cost and caliber of the specialized instrumentation, these services are best facilitated though the centralized TMF. Additional value added is that all Transgenic and Knockout Projects were successful in 2014, resulting in several lines of each desired transgenic or knockout strain. The Facility's 100% success rate attests to its high technical standards and rigorous quality control procedures. Cryopreservation services offered by the TMF provides valuable insurance against loss of irreplaceable mouse lines. The TMF is advised by a dedicated Facility Advisory Committee (FAC) that meets annually. Recommendations from the FAC are directed to a governing Facility Parent Oversight Committee that serves to ensure that the TMF continues to have the necessary resources to provide the highest quality services for Cancer Center members. Demand for services is expected to increase in the next cycle of the CCSG due to plans to recruit in all 5 Programs, and new demand from Cancer Center members at TU. Additionally, TMF services will continue to be available to two nearby institutions, the Wistar Institute and TJU.